A Drug Drug Interaction (DDI) Study of Baricitinib (LY3009104) and Digoxin in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01859078
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arm: 1
• Duration (Months): 3
• Patients Per Site Per Month: 9.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effect of baricitinib on the levels of digoxin in the blood stream and how long it takes the body to remove digoxin. This study will also look at how safe and well-tolerated baricitinib is when given at the same time as digoxin in healthy participants. This study will last approximately 3-4 weeks.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Baricitinib; Drug: Digoxin	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Baricitinib on the Pharmacokinetics of Digoxin in Healthy Subjects
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Baricitinib + Digoxin Digoxin - 0.5 milligrams (mg) administered orally, twice daily (BID), 12 hours apart on Day 1. Then, 0.25 mg administered orally, once daily (QD) on Days 2 through 16. Baricitinib - 10 mg administered orally, QD, on Days 8 through 16.	Drug: Baricitinib; Administered orally; Other Names: LY3009104 ; Drug: Digoxin; Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCτ) of Digoxin [Predose up to 24 hours post-dose on Days 7 and 16]

2. PK: Maximum Concentration (Cmax) of Digoxin [Predose up to 24 hours post-dose on Days 7 and 16]

3. PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin [Predose up to 24 hours post-dose on Days 7 and 16]

Secondary Outcome Measures

1. PK: Amount of Drug Excreted Unchanged During 1 Dosing Interval (Aeτ) of Digoxin [0 to 24 hours post-dose on Days 7 and 16]

2. PK: Renal Clearance (CLr) of Digoxin [Predose to 24 hours post-dose on Days 7 and 16]

   CLr is the volume of plasma from which study drug is completely removed by the kidney in a given time and is calculated as Aeτ divided by AUCτ.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Are overtly healthy males or females, as determined by medical history and physical examination

• Women not of child-bearing potential

• Menopausal women

• Have a body mass index of 18.0 to 29.0 kilograms per square meter (kg/m^2)

Exclusion Criteria:

• Women who are lactating

• Have previously completed or withdrawn from this study or any other study investigating baricitinib

• Currently enrolled in, have completed or discontinued within the last 90 days from a clinical trial involving an investigational product

• Have a pulse rate less than 50 beats per minute (bpm) at screening

• Have a current or recent history (less than 30 days prior to screening and/or less than 45 days prior to Day -1) of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection

• Have an absolute neutrophil count less than 2000 cells/microliter (2×10^9/liter) at screening or Day -1

• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies

• Have been exposed to a live vaccine within 12 weeks prior to the first dose or expected to need/receive a live vaccine

• Intend to use over-the-counter or prescription medication and/or herbal supplements within 14 days prior to dosing and during the study

• Have used or intend to use any drugs or substances that are known to be substrates, inducers, or inhibitors of P-glycoprotein (P-gp) within 30 days prior to dosing and throughout the study

• Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Leeds	West Yorkshire	United Kingdom	LS2 9LH

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri, 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01859078
• Other Study ID Numbers: 14609; I4V-MC-JAGL
• First Posted: May 21, 2013
• Last Update Posted: Jun 6, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Digoxin

Study Results

Participant Flow

Arm/Group Title	Baricitinib + Digoxin
Arm/Group Description	Digoxin - 0.5 milligrams (mg) administered orally, twice daily (BID), 12 hours apart on Day 1. Then, 0.25 mg administered orally, once daily (QD) on Days 2 through 16. Baricitinib - 10 mg administered orally, QD, immediately prior to digoxin on Days 8 through 16.
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Baricitinib + Digoxin
Arm/Group Description	Digoxin - 0.5 mg administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 16. Baricitinib - 10 mg administered orally, QD, immediately prior to digoxin on Days 8 through 16.
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.4 (11.3)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	28 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	28 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	24 85.7%
More than one race	3 10.7%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	28 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCτ) of Digoxin
Time Frame	Predose up to 24 hours post-dose on Days 7 and 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug and had PK data to calculate AUCτ. Participants were analyzed based on the treatment they received.

Arm/Group Title	Digoxin Only	Baricitinib + Digoxin
Arm/Group Description	0.5 mg digoxin administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 7.	10 mg baricitinib administered orally, QD, immediately prior to 0.25 mg digoxin administered orally, QD on Days 8 through 16.
Measure Participants	28	28
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*h/mL)]	18.7 (18)	16.8 (20)

2. Primary Outcome

Title	PK: Maximum Concentration (Cmax) of Digoxin
Time Frame	Predose up to 24 hours post-dose on Days 7 and 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug and had PK data to calculate Cmax. Participants were analyzed based on the treatment they received.

Arm/Group Title	Digoxin Only	Baricitinib + Digoxin
Arm/Group Description	0.5 mg digoxin administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 7.	10 mg baricitinib administered orally, QD, immediately prior to 0.25 mg digoxin administered orally, QD on Days 8 through 16.
Measure Participants	28	28
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	2.04 (23)	1.80 (20)

3. Primary Outcome

Title	PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin
Time Frame	Predose up to 24 hours post-dose on Days 7 and 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug and had PK data to calculate tmax. Participants were analyzed based on the treatment they received.

Arm/Group Title	Digoxin Only	Baricitinib + Digoxin
Arm/Group Description	0.5 mg digoxin administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 7.	10 mg baricitinib administered orally, QD, immediately prior to 0.25 mg digoxin administered orally, QD on Days 8 through 16.
Measure Participants	28	28
Median (Full Range) [hours (h)]	1.00	1.00

4. Secondary Outcome

Title	PK: Amount of Drug Excreted Unchanged During 1 Dosing Interval (Aeτ) of Digoxin
Time Frame	0 to 24 hours post-dose on Days 7 and 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug and had PK data to calculate Aeτ. Participants were analyzed based on the treatment they received.

Arm/Group Title	Digoxin Only	Baricitinib + Digoxin
Arm/Group Description	0.5 mg digoxin administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 7.	10 mg baricitinib administered orally, QD, immediately prior to 0.25 mg digoxin administered orally, QD on Days 8 through 16.
Measure Participants	28	28
Geometric Mean (Geometric Coefficient of Variation) [milligrams (mg)]	0.177 (18)	0.155 (22)

5. Secondary Outcome

Title	PK: Renal Clearance (CLr) of Digoxin
Description	CLr is the volume of plasma from which study drug is completely removed by the kidney in a given time and is calculated as Aeτ divided by AUCτ.
Time Frame	Predose to 24 hours post-dose on Days 7 and 16

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug and had PK data to calculate CLr. Participants were analyzed based on the treatment they received.

Arm/Group Title	Digoxin Only	Baricitinib + Digoxin
Arm/Group Description	0.5 mg digoxin administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 7.	10 mg baricitinib administered orally, QD, immediately prior to 0.25 mg digoxin administered orally, QD on Days 8 through 16.
Measure Participants	28	28
Geometric Mean (Geometric Coefficient of Variation) [Liters/hour (L/h)]	9.46 (20)	9.20 (18)

Adverse Events

Arm/Group Title	Digoxin Only		Baricitinib + Digoxin
Arm/Group Description	0.5 mg digoxin administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 7.		10 mg baricitinib administered orally, QD, immediately prior to 0.25 mg digoxin administered orally, QD on Days 8 through 16.
All Cause Mortality
	Digoxin Only		Baricitinib + Digoxin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Digoxin Only		Baricitinib + Digoxin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Digoxin Only		Baricitinib + Digoxin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/28 (35.7%)		6/28 (21.4%)
Gastrointestinal disorders
Diarrhoea	1/28 (3.6%)	1	3/28 (10.7%)	3
General disorders
Fatigue	2/28 (7.1%)	2	1/28 (3.6%)	1
Nervous system disorders
Headache	5/28 (17.9%)	5	2/28 (7.1%)	3
Renal and urinary disorders
Pollakiuria	3/28 (10.7%)	3	0/28 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.